Prion diseases are neurodegenerative disorders that are caused by misfolding of the prion protein (PrP) from a normal cellular protein (PrP^C) to a protease-resistant isoform (PrP^Sc). This conversion is thought to relate to Cu²⁺ binding to histidine residues; however, the aggregation mechanism is not fully understood due to the physical properties of PrP, such as its solubility or aggregation in vitro. In the present study, we focused on the importance of the role of the C-terminal region of PrP in structural conversion and aggregation. The physical and physiological properties of the synthetic fragment peptide human-PrP180-192 (hPrP180-192) were evaluated by circular dichroism (CD) spectra, high performance liquid chromatography (HPLC), Affinix quartz-crystal microbalance (QNμ), and Thioflavin-T staining. The secondary structure of hPrP180-192 changed from a random coil to a β-sheet in Cu²⁺ free buffer. In addition, we observed molecular interactions in hPrP180-192, and aggregation with itself, which was inhibited by Cu²⁺. We concluded that the C-terminal region of PrP, including hPrP180-192, may play an important role for the conversion of PrP^C to PrP^Sc. These results support the seed theory aggregation mechanism for PrP.